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Recruiting NCT07448623

A Research Study to Look at the Distribution and Effects of Coramitug on Amyloid Deposits in Heart Tissue Using PET/CT Imaging in People With ATTR Amyloidosis.

Phase I Interventional Transthyretin Amyloid Cardiomyopathy

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Coramitug.
Who it may be relevant to
Registry conditions: Transthyretin Amyloid Cardiomyopathy. Basic parameters: from 60 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
Netherlands
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

An Open-label Study to Evaluate the Biodistribution of 89Zr-coramitug and Investigate the Effects of Coramitug on Depleting TTR Amyloid Deposits in Myocardial Tissues Using PET/CT Imaging in Participants With ATTR-CM

Overview

The study is conducted in participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM), a heart disease that occurs in people with the disease ATTR amyloidosis. The purpose of this study is to see how radioactively labelled coramitug is taken up by the heart after administration through an infusion (Cohort 1), and to understand the extent to which coramitug can be displaced by radioactively labelled coramitug (Cohort 2). In this study it will also be investigated how safe coramitug is and how well it is tolerated when it is used by participants with ATTR-CM. Coramitug is potentially a new medicine for participants with ATTR-CM. Coramitug is a monoclonal antibody that potentially binds to the accumulations of the transthyretin protein and promotes its removal from the heart. It may also prevent the formation of clumps and may help with clearing existing clumps of the abnormal protein. The study will take a maximum of 85 days (for Cohort 1) or 106 days (for Cohort 2) when participating in Period A from the screening until the follow-up visit.

Interventions

  • Drug Coramitug
    Coramitug will be administered intravenously

Primary outcome measures

  • Mean Standard Uptake Value Ratio (SUVRmean) in myocardium [Time frame: Day 1-day 8]
  • Net uptake rate constant (Ki) in myocardium [Time frame: 0 to 168 hours]
  • Change in SUVRmean in myocardium [Time frame: From baseline to week 52 (day 364), or week 60 (day 420) if there is no uptake expected/observed when both unradiolabelled and radiolabelled compounds are administered together]
Secondary outcome measures (10)
  • Maximum Plasma Concentration (Cmax) [Time frame: 0 to 168 hours]
  • Time at which maximum plasma concentration is observed (Tmax) [Time frame: 0 to 168 hours]
  • Area under the curve (AUC) [Time frame: 0 to 168 hours]
  • Terminal half-life (T1/2) [Time frame: 0 to 168 hours]
  • Cmax [Time frame: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
  • Tmax [Time frame: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
  • AUC [Time frame: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
  • T1/2 [Time frame: 0 to 168 hours for cohort 1, 0 to 672 hours for cohort 2]
  • Number of Treatment Emergent Adverse Events (TEAE) [Time frame: From day 1 to day 8 in cohort 1 or day -1 to day 28 for cohort 2]
  • Number of Treatment Emergent Adverse Events [Time frame: From baseline to week 52 (day 364), or week 64 (day 448) if there is no uptake expected/observed when both unradiolabelled and radiolabelled compounds are administered together]

Eligibility criteria

Inclusion criteria

  • Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
  • Male or female.
  • Age greater than or equal to (≥) 60 years or above at the time of signing the informed consent.
  • For participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM):
  • Have an established diagnosis of ATTR-CM, with either wild-type Transthyretin (TTR) or variant TTR genotype (ATTRwt) or (ATTRv), with cardiac amyloid infiltration, increased left ventricular (LV) wall thickness, \& heart failure (HF):

a) Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR ii. Grade 2 or Grade 3 cardiac uptake at pyrophosphate/3,3-diphosphono-1,2-propanodicarboxylic acid/hydroxymethylene diphosphonate (PYP/DPD/HMDP) scintigraphy with Single-Photon Emission Computed Tomography (SPECT/CT) combined with an extracardiac biopsy positive for TTR amyloid, OR iii. Grade 2 or Grade 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combined with normal serum free light chain ratio \& negative serum \& urine immunofixation (Serum Immunofixation \[SPIE\] and Urine Immunofixation \[UPIE\]) Note: Bone tracer scintigraphy using 99m technetium (Tc)-labelled pyrophosphate (99mTc-PYP)/99mTc-labelled 3,3-diphosphono-1,2- propanodicarboxylic acid (99mTc-DPD)/99mTc-labeled hydroxymethylene diphosphonate (99m-Tc-HMDP) b. Increased LV wall thickness, as assessed by echocardiography showing LV posterior and septal wall thickness greater than or equal to (≥)13 millimeter (mm) for women and ≥ 14 mm for men (Note: Pre-existing echocardiogram up to 2 years old can be used).

c. Chronic HF with: i. At least 1 documented hospitalisation for HF occurring greater than (>) 3 months but less than (<) 2 years, OR ii. History of HF manifested by signs or symptoms of volume overload or elevated intracardiac pressures (e.g., elevated jugular venous pressure, shortness of breath, signs of pulmonary con-gestion on x-ray or auscultation, or peripheral oedema) requiring ongoing treatment with a loop diuretic.

Exclusion criteria

  • Known or suspected hypersensitivity to study intervention(s) or related products.
  • Previous participation in this study. Participation is defined as signed informed consent.
  • Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential.
  • Current participation (i.e., signed informed consent) in any other interventional clinical study.
  • Participation in research studies involving exposure to radiation within a year preceding the screening period in this study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

Netherlands · 1 center
  • ICON - location Groningen — Groningen

Identifiers

NCT: NCT07448623 · NN6019-7853 · U1111-1316-9198 · 2024-519372-22

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗